The effect of neonatal treatment with a gonadotropin releasing hormone (GnRH) antagonist on sexual and immune system development and function is being assessed in male monkeys maintained in a social group under natural lighting conditions. The disruption of neonatal activity of the hypothalamic-pituitary-testicular axis retarded sexual development, but did permanently block the achievement of reproductive competence. Social rank was a major factor in determining the tempo of sexual maturation, and the influence of this regulatory factor could not be overriden by neonatal treatment with testosterone. Treated animals showed abnormal developmental patterns of lymphocyte subsets, and as adults were immunosuppressed. Cell- and humoral-mediated immunity of treated animals were subnormal, but social rank did not impact on immune function. Immune function varied with season in all animals, but this seasonality was especially pronounced in control monkeys. The results s upport th e contention that the neonatal period is a critical interval in development, and that endocrine perturbations during this period alters sexual maturation and the ability of the animal to respond to antigenic challenge. It also appears that immune function in the rhesus monkey varies with seasons, an effect that may be mediated by circannual fluctuations in immunoactive hormones. FUNDING NIH / HD2643 $113,627 4/01/95 - 3/31/99 PUBLICATIONS *Gould, K.G., Akinbami, M.A. and Mann, D.R. Effect of neonatal treatment with a gonadotropin releasing hormone antagonist on developmental changes in circulating lymphocyte subsets A longitudinal study in male rhesus monkeys. Developmental and Comparative Immunology 22:457-467, 1998. Mann, D.R., Howie, S., Paulsen, D.R., Akinbami, M.A., Lunn, S.F. and Fraser, H.M. Changes in lymphoid tissue after treatment with a gonadotropin releasing hormone antagonist in the neonatal marmoset (Callithrix jacchus). Amer. J. Reprod. Immunol. 39:256-265, 1998. *Mann, D.R., Akinbami, M.A., Gould, K.G., Paul, K. and Wallen, K. Sexual maturation in male rhesus monkeys Importance of neonatal testosterone exposure and social rank. J. Endocrinology, 156:493-501, 1998.